Use of a standard course of topical fluorouracil 5% cream is not associated with a significant improvement in photoaging, which may be the result of limitations in the photonumeric scales currently used to validate the effects of the treatment, according to results of a randomized clinical trial published in JAMA Dermatology.
The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial (VAKCCT) sought to assess the chemopreventive effects of a standard course of topical fluorouracil cream. Photographs of patients (N=932) were taken at baseline and then again at numerous times throughout the study, for up to 4 years.
In the current ad hoc secondary analysis of VAKCCT, 2 independent dermatologists graded the photographs using 4 validated photonumeric scales. The analysis included 281 participants who were randomly assigned to treatment with topical fluorouracil or placebo. The dermatologists looked at a total of 3042 photographs of the participants and evaluated them at baseline, at 6 months, at 12 months, and at 18 months. Patients applied topical fluorouracil 5% cream or a vehicle control cream to their face and ears twice daily for 2 to 4 weeks, for a total of 28 to 56 doses.
The main study outcome was the effect of a standard course of fluorouracil on the extent of photodamage. The study population was 97.5% male, and all participants were white. Mean patient age was 71.5 years.
No significant differences in photodamage were observed between the 2 treatment groups from baseline to 6 months, baseline to 12 months, and baseline to 18 months, using each of the 4 photonumeric scales (Griffiths scale: P =.93, P =.24, and P =.08, respectively;  Allergan forehead lines scale: P =.67, P =.43, and P =.34, respectively;  melomental fold scale: P =.87, P =.73, P =.20, respectively; and  crow’s feet scale: P =.12, P =.30, and P =.50, respectively).
According to the researchers, the lack of improvement in photoaging with a standard course of topical fluorouracil may be attributable to an actual lack of effect in photodamage or to limitations in the photonumeric scales used. The development of photonumeric scales that are capable of capturing such manifestations of photoaging as lentigines, hyperpigmentation, and telangiectasias warrants investigation.
Korgavkar K, Lee KC, Weinstock MA; Veterans Affairs Keratinocyte Carcinoma Chemoprevention (VAKCC) Trial Group. Effect of topical fluorouracil cream on photodamage: secondary analysis of a randomized clinical trial [published online September 6, 2017]. JAMA Dermatol. doi: 10.1001/jamadermatol.2017.2578